Moraxella catarrhalis is a gram-negative mucosal pathogen of the human respiratory tract. Although little information is available regarding the initial steps of M. catarrhalis pathogenesis, this organism must be able to colonize the human mucosal surface in order to initiate an infection. Type IV pili (TFP), filamentous surface appendages primarily comprised of a single protein subunit termed pilin, play a crucial role in the initiation of disease by a wide range of bacteria. We previously identified the genes that encode the major proteins involved in the biosynthesis of M. catarrhalis TFP and determined that the TFP expressed by this organism are highly conserved and essential for natural transformation. We extended this initial study by investigating the contribution of TFP to the early stages of M. catarrhalis colonization. TFP-deficient M. catarrhalis bacteria exhibit diminished adherence to eukaryotic cells in vitro. Additionally, our studies demonstrate that M. catarrhalis cells form a mature biofilm in continuous-flow chambers and that biofilm formation is enhanced by TFP expression. The potential role of TFP in colonization by M. catarrhalis was further investigated using in vivo studies comparing the abilities of wild-type M. catarrhalis and an isogenic TFP mutant to colonize the nasopharynx of the chinchilla. These results suggest that the expression of TFP contributes to mucosal airway colonization. Furthermore, these data indicate that the chinchilla model of nasopharyngeal colonization provides an effective animal system for studying the early steps of M. catarrhalis pathogenesis.Moraxella catarrhalis, a gram-negative mucosal pathogen of the human respiratory tract, can also reside as a nasopharyngeal commensal. M. catarrhalis is capable of causing multiple diseases of the upper respiratory tract, including sinusitis, laryngitis, and acute and chronic otitis media, predominantly in pediatric populations, as well as recurrent exacerbations of chronic obstructive pulmonary disease in adults with underlying lung disease (31, 41). As with many other pathogenic bacteria, adherence to host tissues and subsequent colonization of the respiratory tract mucosa are believed to be essential prior to the development of M. catarrhalis infections.M. catarrhalis expresses a number of cell surface components that have been postulated to be involved in bacterial virulence (reviewed in references 29 and 41). However, in vivo studies of M. catarrhalis pathogenesis have been limited by the lack of an effective animal model to investigate bacterial colonization of the upper respiratory tract epithelium. Even with the most prevalently used model system, the mouse pulmonary clearance model, M. catarrhalis is markedly cleared from the site within 6 h and the organism is almost completely eradicated by 24 h (40). Although little information is available regarding the actual steps involved in the pathogenesis of M. catarrhalis infections in vivo, it is clear that this organism must attach to the mucosal surface in order to ...